The insufficient delivery of therapeutic molecules to tumour cells is one of the reasons for the failure of treatment strategies for cancer. There is, therefore, a great need for the identification of cellular vectors that specifically approach cancer stem cells to deliver therapeutic molecules. Recent studies have demonstrated the tropism of normal neuronal stem cells and bone marrow (BM) derived stem cells for cancer. Implanted neuronal stem cells surrounded the expanding brain tumour mass and even attached to the distantly infiltrating tumour cells. It has been shown that this homing property could be exploited to deliver various therapeutic agents to tumours.
The tropism of stem cells for cancer is not limited to the stem cells of neuroectodermal origin or central nervous system. Several recent studies have shown that bone marrow (BM) mesenchymal stem cells (MSC) could be used as vehicles for the treatment of brain tumours.
However, MSC might undergo spontaneous transformation following long-term in vitro culture, causing concerns about their tumorigenicity and subsequent use for clinical therapy.
Another BM-derived stem cell population that may have the potential to be used to target cancer stem cells comprises haematopoietic stem cells. Haematopoietic stem cells (HSC) participate in tissue regeneration by promoting immune response and/or differentiating into functional cells involved in the repair of damaged tissue. HSC are CD34+ and CD133+ and have the advantage that they can be prospectively isolated from BM-aspirate or mobilised peripheral blood as a morphologically and immunophenotypically defined cell population. They possess the ability to self-renew and are an unlimited source of potential cellular vectors.
HSC express the chemokine receptor CXCR4. The ligand of this receptor, stromal-derived growth factor-1 (SDF-1), was found to be expressed by solid tumours, which could provide the basis for directing and homing of reparative cells such as HSC to tumours.
The SDF-1 and CXCR4 axis is an important regulator of stem cell trafficking and migration and also regulates cell chemotaxis and adhesion. It has been suggested that HSC have a tropism for cancer. Their trophic effects may have important clinical use, as HSC could be used as vehicles for the delivery of therapeutic agents to the site of the tumours. Moreover, modified HSC can produce high concentrations of anti-tumour agents directly within the tumour mass, impact tumour growth and progression and deliver site-specific cytotoxic agents.
There remains a great need for ways to improve the success of anti-cancer treatments, and treatments of anti-proliferative disorders in general.